アブストラクト（42巻1号：神奈川歯学）

神奈川歯学

Japanese

Title　： 細菌内毒素による破骨細胞の分化誘導におけるMAPKの役割に関する研究
Subtitle　：
Authors　： 石川恵里子, 渡辺清子
Authors（kana）　：
Organization　： 神奈川歯科大学感染制御学講座・微生物学分野
Journal　： 神奈川歯学
Volume　： 42
Number　： 1
Page　： 1-12
Year/Month　： 2007 / 6
Article　： 原著
Publisher　： 神奈川歯科大学学会
Abstract　： 緒言 成人性歯周炎はPorphyromonas gingivalisを初めとする歯肉縁下プラーク中の偏性嫌気性グラム陰性菌の増加により引き起こされる歯槽骨の吸収を主な病状とする疾患である1～5). 特にグラム陰性菌の外膜成分であるリボ多糖(Lipopolysaccharide;LPS)が, 歯周疾患における重要な病原因子として歯槽骨の吸収を促進する因子の一つと考えられている6～10). 細菌内毒素成分であるLPSあるいはその活性画分であるlipid Aは, マクロファージや血管内皮細胞, あるいは線維芽細胞を刺激して様々な炎症性サイトカインの産生を誘導しており, 破骨細胞の分化, 成熟に関与している. すなわち, IL-1βや腫瘍壊死因子(TNF-α)は歯槽骨の吸収に関して重要な役割を担っており, 直接的に破骨細胞を刺激して骨吸収を促進することが報告されている11～13). IL-1β, IL-6, TNF-α等は炎症性サイトカインといわれているが, 単に炎症を誘導するだけではなく顕著な破骨細胞性骨吸収の促進作用を持っており14, 15), 骨吸収性サイトカインとも呼ばれている.
Practice　： 歯科学
Keywords　： 細菌内毒素(LPS), MAPK, 破骨細胞

English

Title　： The role of MAPK on the osteoclast differentiation and function induced by bacterial endotoxin
Subtitle　：
Authors　： Eriko ISHIKAWA, Kiyoko WATANABE
Authors（kana）　：
Organization　： Department of Oral Microbiology, Kanagawa Dental College
Journal　： Kanagawa Shigaku
Volume　： 42
Number　： 1
Page　： 1-12
Year/Month　： 2007 / 6
Article　： Original article
Publisher　： Kanagawa Odontological Society
Abstract　： Adult periodontitis is characterized by gingival inflammation and alveolar bone resorption. Bacterial endotoxin (lipopolysaccharide ; LPS), the cell-surface component of Gram-negative bacteria, is considered to cause inflammatory bone loss by stimulating monocytes and macrophages to produce various inflammatory cytokines such as IL-1, TNF-α and IL-6. Recent studies indicate that LPS induces inflammatory cytokine production and osteoclast differentiation through Toll-like receptor 4 (TLR4) and stimulation of it by LPS activates mitogen-activated protein kinase (MAPK) pathway. In this study, we investigated the roles of MAPK-mediated signals in the differentiation, maturation and function of osteoclasts. E. coli LPS remarkably induced IL-1β and TNF-α production in a dose-dependent manner. Pretreatment of murine macrophages with SB203580 or SP600125, which blocks p38 or JNK activity, respectively, significantly inhibited cytokine production. On the other hand, U0126, a specific inhibitor of MEK1/2, had no effect on cytokine production. In order to clarify the induction of osteoclast differentiation by E. coli LPS, the LPS was added to co-cultured cells of MC3T3-G2/PA6 and mice bone marrow cells. The number of colonies containing tartrateresistant acid phosphatase (TRAP) positive cells stimulated with LPS was comparable tothe control cultures and all the MAPK inhibitors did not affect the colony formation. In contrast, treatment of co-cultured cells with SB203580 or U0126 significantly reduced the number of TRAP-positive multinuclear cells (MNCs), which was markedly increased by the addition of LPS. In order to estimate osteoclast function, aliquots of crude osteoclast preparation were placed on dentine slices and cultured with or without E. coli LPS for 7 days. The expansion of pit formation was observed when the osteoclasts were incubated with E. coli LPS and SB203580 treatment explicitly suppressed pit-forming activity of osteoclast preparation. These results suggest that p38 plays important roles in the osteoclast differentiation and function induced by E. coli LPS
Practice　： Dentistry
Keywords　： LPS, MAPK